Efficacy of lonidamine combined with different DNA-damaging agents in the treatment of the MX-1 tumor xenograft

The a.c. conductivity of the proteins lysozyme and subtilisin, both in their active and inactive or inhibited forms were determined theoretically. For this, quantum mechanical calculations and a random walk theory were used. The conclusions are that these enzymatic proteins can easily transport electrons which is most probably important in their role as catalysators of biochemical reactions. The electron transport is sensitive to three-dimensional changes of the active sites of these enzymes which have more flexibility than the whole molecule. Therefore, the flexibility of the active sites of enzyme catalysts is not only important for the conformational fitting with the reactants, but also strongly influences the transport in biochemical reactions.     

Distinct Tomato Cultivars Are Characterized by a Differential Pattern of Biochemical Responses to Drought Stress

Future climate scenarios suggest that crop plants will experience environmental changes capable of affecting their productivity. Among the most harmful environmental stresses is drought, defined as a total or partial lack of water availability. It is essential to study and understand both the damage caused by drought on crop plants and the mechanisms implemented to tolerate the stress. In this study, we focused on four cultivars of tomato, an economically important crop in the Mediterranean basin. We investigated the biochemical mechanisms of plant defense against drought by focusing on proteins specifically involved in this stress, such as osmotin, dehydrin, and aquaporin, and on proteins involved in the general stress response, such as HSP70 and cyclophilins. Since sugars are also known to act as osmoprotectants in plant cells, proteins involved in sugar metabolism (such as RuBisCO and sucrose synthase) were also analyzed. The results show crucial differences in biochemical behavior among the selected cultivars and highlight that the most tolerant tomato cultivars adopt quite specific biochemical strategies such as different accumulations of aquaporins and osmotins. The data set also suggests that RuBisCO isoforms and aquaporins can be used as markers of tolerance/susceptibility to drought stress and be used to select tomato cultivars within breeding programs.     

Inhibitors of Mitochondrial Human Carbonic Anhydrases VA and VB as a Therapeutic Strategy against Paclitaxel-Induced Neuropathic Pain in Mice

Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca²⁺ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs.     

Epigenetic and Genetic Factors Related to Curve Progression in Adolescent Idiopathic Scoliosis: A Systematic Scoping Review of the Current Literature

Adolescent idiopathic scoliosis (AIS) is a progressive deformity of the spine. Scoliotic curves progress until skeletal maturity leading, in rare cases, to a severe deformity. While the Cobb angle is a straightforward tool in initial curve magnitude measurement, assessing the risk of curve progression at the time of diagnosis may be more challenging. Epigenetic and genetic markers are potential prognostic tools to predict curve progression. The aim of this study is to review the available literature regarding the epigenetic and genetic factors associated with the risk of AIS curve progression. This review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was carried out in January 2022. Only peer-reviewed articles were considered for inclusion. Forty studies were included; fifteen genes were reported as having SNPs with significant association with progressive AIS, but none showed sufficient power to sustain clinical applications. In contrast, nine studies reporting epigenetic modifications showed promising results in terms of reliable markers. Prognostic testing for AIS has the potential to significantly modify disease management. Most recent evidence suggests epigenetics as a more promising field for the identification of factors associated with AIS progression, offering a rationale for further investigation in this field.     

Stimulation of the activity of the IAA-oxidising enzyme - system in Lens culinaris roots by dalapon and perfluidone

The activity of IAA-oxidising enzymes from Lens roots is enhanced in vitro by dalapon (2,2-dichloropropionic acid) and perfluidone (1,1,1 -trifluoro-N-[2-methyl-4-(phenylsulphonyl)phenyl]methanesulphonamide). When concentrations are greater than 10^?8 M, both these herbicides act as activators. In vivo higher levels of the enzymatic activity are obtained when seed germination is carried out in the presence of 10^?5 M perfluidone or 10^?3 M dalapon. Gas-liquid chromatography is used for IAA determination.     

Performance evaluation of TCP‐based applications over DVB‐RCS DAMA schemes

Transmission Control Protocol (TCP) performance over Digital Video Broadcasting—Return Channel via Satellite (DVB‐RCS) standard is greatly affected by the total delay, which is mainly due to two components, propagation delay and access delay. Both are significant because they are dependent on the long propagation path of the satellite link. The former is intrinsic and due to radio wave propagation over the satellite channel for both TCP packets and acknowledgements. It is regulated by the control loop that governs TCP. The latter is due to the control loop that governs the demand assignment multiple access (DAMA) signalling exchange between satellite terminals and the network control center, necessary to manage return link resources. DAMA is adopted in DVB‐RCS standard to achieve flexible and efficient use of the shared resources. Therefore, performance of TCP over DVB‐RCS may degrade due to the exploitation of two nested control loops also depending on both the selected DAMA algorithm and the traffic profile. This paper analyses the impact of basic DAMA implementation on TCP‐based applications over a DVB‐RCS link for a large set of study cases. To provide a detailed overview of TCP performance in DVB‐RCS environment, the analysis includes both theoretical approach and simulation campaign. Copyright © 2009 John Wiley & Sons, Ltd.     

Robust security framework for DVB‐RCS satellite networks (RSSN)

Satellites represent a solution for Internet access in locations with no other telecom infrastructures, for example, on high mobility platforms such as planes, ships or high‐speed trains, or for disaster recovery applications. However, due to peculiar characteristics, satellite networks are prone to different security threats. In this paper, we introduce a novel, robust security architecture for securing digital video broadcasting‐return channel via satellite satellite networks, inspired by the robust security mechanism available in the Institute of Electrical and Electronic Engineers (IEEE) 802.11i wireless local area network. We propose an efficient authentication and key management mechanism, which is exploited through three round‐trips only, demonstrating that it is as secure as IEEE 802.11i. Furthermore, the simulation results show that the proposed security framework needs a very small data overhead and shows better performance than internet protocol security (IPSec), which is commonly used as an end‐to‐end security solution over internet protocol satellite networks. Copyright © 2015 John Wiley & Sons, Ltd.     

Transport layer enhancements on a satellite‐based mobile broadband system for high‐speed trains

The great diffusion of wireless portable and handheld devices, along with the growing availability of applications on the Internet, led to a significant increase in the demand of access. Users require to continue business or private activities when moving, with performance at least comparable with that experienced over fixed networks. A very interesting scenario encompasses broadband and uninterrupted access over high‐speed trains. Developments of new telecommunication standards as well as innovative network architectures give the potential to fully match the aforementioned requirements. Nevertheless, there is a significant number of issues, especially related to system integration, mobility management, and propagation channel conditions, that need a careful analysis with the aim to support the design of real systems. This paper deals with this challenging scenario proposing a satellite‐based architecture in which DVB‐S2 and DVB‐RCS standards, MIPv6 at layer 3 (for handover management), and an enhanced TCP version at layer 4, named TCP Noordwijk, allow to achieve good performance. An NS‐2 enhanced simulator has supported the whole analysis. Results show the effectiveness of the proposed scheme against different modulation and coding configurations and compared with a selected set of TCP‐enhanced versions. Copyright © 2012 John Wiley & Sons, Ltd.     

Solar-blind UV photodetectors for large area applications

In this paper, we extensively investigate a family of solar-blind thin-film photodetectors optimized for the ultraviolet spectrum (UV). The devices are p-i-n structures made of hydrogenated amorphous silicon (a-Si:H) and silicon carbide (a-SiC:H) on a glass substrate. At room temperature the photodetectors exhibit values of quantum efficiency of 20% at λ=187 nm, and are transparent to visible radiation. The excellent sensitivity of the device at short wavelengths is explained within the framework of a diffusive model of transport, taking into account the effects of hot carrier relaxation. The rejection of visible light is obtained with an appropriate design of the energy gap and intrinsic layer thickness. The great advantage of this technology lies in the possibility to produce low-cost, large-area arrays of photodetectors     

OCTN1: A Widely Studied but Still Enigmatic Organic Cation Transporter Linked to Human Pathology and Drug Interactions

The Novel Organic Cation Transporter, OCTN1, is the first member of the OCTN subfamily; it belongs to the wider Solute Carrier family SLC22, which counts many members including cation and anion organic transporters. The tertiary structure has not been resolved for any cation organic transporter. The functional role of OCNT1 is still not well assessed despite the many functional studies so far conducted. The lack of a definitive identification of OCTN1 function can be attributed to the different experimental systems and methodologies adopted for studying each of the proposed ligands. Apart from the contradictory data, the international scientific community agrees on a role of OCTN1 in protecting cells and tissues from oxidative and/or inflammatory damage. Moreover, the involvement of this transporter in drug interactions and delivery has been well clarified, even though the exact profile of the transported/interacting molecules is still somehow confusing. Therefore, OCTN1 continues to be a hot topic in terms of its functional role and structure. This review focuses on the most recent advances on OCTN1 in terms of functional aspects, physiological roles, substrate specificity, drug interactions, tissue expression, and relationships with pathology.